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Clinical Research

Hypoxia and exercise interactions on skeletal muscle insulin sensitivity in obese subjects with metabolic syndrome: results of a randomized controlled trial

Abstract

Background

Physical activity improves insulin sensitivity in obesity. Hypoxia training is claimed to augment this effect. We tested the hypothesis that normobaric hypoxia training would improve insulin sensitivity in obese patients with metabolic syndrome.

Methods

In a randomized controlled trial, 23 obese men with metabolic syndrome who were not informed of the FiO2 conditions underwent a 6-week physical exercise intervention under ambient (n = 11; FiO2 21%) conditions or hypoxia (n = 12; FiO2 15%) using a normobaric hypoxic chamber. Three 60-min sessions of interval training were performed each week at 60% of individual V̇O2max. Assessment of myocellular insulin sensitivity by euglycemic hyperinsulinemic clamp was performed in 21 of these subjects before and after 6 weeks of training. Comprehensive phenotyping also included biopsies of subcutaneous adipose tissues.

Results

The intermittent moderate physical exercise protocol did not substantially change the myocellular insulin sensitivity within 6 weeks under normoxic conditions (ISIClamp: 0.035 (IQR 0.016–0.075) vs. 0.037 (IQR 0.026–0.056) mg* kg−1 *min−1/(mU* l−1); p = 0.767). In contrast, ISIClamp improved during hypoxia training (0.028 (IQR 0.018–0.035) vs. 0.038 (IQR 0.024–0.060) mg * kg−1 *min−1/(mU *l−1); p < 0.05). Between group comparison of ISIClamp change revealed a small difference between groups (Cohen's d = 0.26). Within the hypoxic group, improvement of ISIClamp during training was associated with individual increase of circulating vascular endothelial growth factor (VEGF) levels (r = 0.678, p = 0.015), even if mean VEGF levels were not modified by any training condition. Atrial natriuretic peptide (ANP) system components were not associated with increased ISIClamp during hypoxic training.

Conclusions

Physical training under hypoxic conditions could partially augment the favorable effects of exercise alone on myocellular insulin sensitivity in obese men with metabolic syndrome. Concomitant changes in VEGF might represent an underlying pathophysiological mechanism.

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Fig. 1
Fig. 2: ISIClamp before and after a moderate 6-week training under either normobaric normoxic (n = 9) or hypoxic (n = 12) conditions.
Fig. 3: Adipose NPR-A/NPR-C ratio before and after a moderate 6-week training under either normobaric normoxic (n = 9) or hypoxic conditions (n = 12).
Fig. 4

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank Gabriele Rahn, N. Huckauf, and C. Kalischke for excellent technical assistance.

Funding

This research was supported by the Deutsche Forschungsgemeinschaft (LU 435/13-1). KM was supported by the German Diabetes Society (DDG) and the German Ministry for Education and Research (BMBF) by support of the Berlin Institute of Health (BIH).

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NR, MB, LK, AM, TB, and JSM researched data. KM researched data and was primarily responsible for writing the manuscript. TB, MB, SP, AM, LK, JS, and FCL contributed to the discussion and reviewed/edited the manuscript. FCL conceived the study and obtained funding.

Corresponding author

Correspondence to Knut Mai.

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The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

The study protocols were approved by the Institutional Review Board of the Charité Medical School (EA1/140/12) and all subjects gave written informed consent.

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Mai, K., Klug, L., Rakova, N. et al. Hypoxia and exercise interactions on skeletal muscle insulin sensitivity in obese subjects with metabolic syndrome: results of a randomized controlled trial. Int J Obes 44, 1119–1128 (2020). https://doi.org/10.1038/s41366-019-0504-z

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